Author Interviews, Autism, Radiology / 27.01.2015

Gabriel S. Dichter, PhD Associate Professor UNC Departments of Psychiatry and Psychology Carolina Institute for Developmental Disabilities MedicalResearch.com Interview with: Gabriel S. Dichter, PhD Associate Professor UNC Departments of Psychiatry and Psychology Carolina Institute for Developmental Disabilities Medical Research: What is the background for this study? What are the main findings? Dr. Dichter: The background for this study is that although most brain imaging research in autism spectrum disorders has focused on understanding the brain basis of social communication impairments, we know that autism symptoms are pervasive and may include difficulties with irritability, anxiety, mood, and even in some instances aggression or self injurious behaviors.  Additionally, these types of associated features are among the first that prompt parents to bring their child to a pediatrician for an evaluation for a neurodevelopmental disorder, and so we know these symptoms can be deeply troubling to parents.  All of these associated symptoms of autism suggest difficulty with regulating emotional responses, and so our team set out to investigate the brain basis of these difficulties.  We taught participants with and without autism simple strategies to change their emotion responses and then scanned them using functional MRI to measure brain activity when they actively tried to change their emotional responses to pictures of faces.  Our central finding was that although they reported they were able to change their emotional responses, brain imaging findings told us something quite different.  The dorsolateral prefrontal cortex, a part of the brain that controls emotional responses, was underactive in the participants with autism.  Consequently, they were less able to modulate parts of the brain’s limbic system that produces strong emotional responses.  In other words, they had difficulty “turning on the brakes” to control emotional responses.  Finally, the differences we observed in their brain activity predicted the severity of their overall autism symptoms, suggestion a direct linkage between emotion regulation impairments and autism severity. (more…)
Author Interviews, Circadian Rhythm, CMAJ / 27.01.2015

Scott R. Garrison MD PhD Associate Professor, Department of Family Medicine Director, Pragmatic Trials Collaborative Faculty of Medicine University of Alberta EdmontonMedicalResearch.com Interview with: Scott R. Garrison MD PhD Associate Professor, Department of Family Medicine Director, Pragmatic Trials Collaborative Faculty of Medicine University of Alberta Edmonton MedicalResearch: What is the background for this study? What are the main findings? Dr. Garrison: Nocturnal leg cramps (also called rest cramps) are painful muscle tightenings, most often in the legs or feet, that are brought on by rest and often wake the sufferer from sleep. They are very common in older adults and can also occur during pregnancy. Having read anecdotal mention that the rest cramps of pregnancy appeared to be worse in summer we sought cohort level evidence to determine whether the more common presentation of age-related rest cramps was also seasonal. To do this we primarily looked at new quinine starts in the province of British Columbia over a period of several years. British Columbia has a publicly funded health care system and maintains electronic records on all health services, including prescription drugs, provided to its roughly 4.2 million residents. Quinine is approved for the treatment of acute malaria in Canada but is instead almost exclusively used off-label to prevent rest cramps. As such, new quinine starts are an excellent marker for new or escalating cramp burden. We also looked at Internet searches, geographically limited to the USA, for the term “leg cramps” (reflecting public interest) obtained from the Google Trends Search Volume Index Tool. Seasonality for both of these indicators of cramp burden was assessed by determining how well a least squares minimizing sinusoidal model predicted variability. We found that quinine starts and "leg cramp" related Internet queries were both strikingly sinusoidal with a 365-day periodicity (mid-summer high, mid-winter low) and a peak-to-peak variability that is approximately 2/3 of the mean. Seasonality accounted for 88% of the observed monthly variability (p < 0.0001) in quinine starts, and 70% of the observed variability (p < 0.0001) in “leg cramp” related internet searches. (more…)
Author Interviews, Cognitive Issues, HIV / 27.01.2015

Sophie Cohen MD, PhD Student Department of Pediatric Haematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands Cairns Base Hospital Australia MedicalResearch.com Interview with: Sophie Cohen MD, PhD Student Department of Pediatric Haematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands Cairns Base Hospital Australia Medical Research: What is the background for this study? What are the main findings? Response: Since combination antiretroviral therapy (cART) has become widely available for HIV-infected children, the incidence of severe neurological complications has decreased drastically from 30-50% to less than 2%. Unfortunately, even in cART-treated HIV-infected children a range of cognitive problems have been found, such as a lower intelligence quotient (IQ) and poorer visual-motor integration. Importantly, while most HIV-infected children in industrialized countries are immigrants with a relatively low socioeconomic status (SES), cognitive studies comparing HIV-infected children to SES-matched controls are very scarce.  Understanding the prevalence and etiology of cognitive deficits in HIV-infected children is essential because they may result in more pronounced problems, and influence future intellectual performance, job opportunities and community participation. Also, early detection of cognitive impairment might trigger the development of early intervention strategies. In this study we aimed to compare the neuropsychological profile of HIV-infected children to that of healthy controls, matched for age, gender, ethnicity and SES. Also, we aimed to determine the prevalence of cognitive impairment in the HIV-infected group and detect associations between HIV/cART parameters and cognitive performance. We found that the HIV-infected group had a poorer cognitive performance compared with the healthy children on all tested domains (including intelligence, information processing speed, attention, memory, executive- and visual-motor functioning). Using a novel statistical method called Multivariate normative comparison (MNC), we detected a prevalence of 17% with cognitive impairment in the HIV-infected group. Lastly, we found that the center for disease control (CDC) clinical category at HIV diagnosis was inversely associated with verbal IQ (CDC C: coefficient -22.98, P=0.010). (more…)
Author Interviews, Primary Care, Radiology / 27.01.2015

Christine Hughes Hadley Hart Group, Chicago, IllinoisMedicalResearch.com Interview with: Christine Hughes Hadley Hart Group, Chicago, Illinois Medical Research: What is the background for this study? Response: Value in healthcare is a popular topic today. Yet no clear value measures have been developed which could be used in policy decisions on reimbursement for diagnostic imaging procedures.  Within the imaging sector it is a given that imaging has value.  However efforts to articulate that value to payers and policy makers and others outside the sector have come up short.   We did conduct qualitative research with radiologists but during this process of mapping a value chain it became clear that those M.D.s who use the data that radiology provides to make decisions on patient care could better speak to imaging’s value.  And primary care because of the gatekeeper status for all types of care seemed appropriate. Medical Research: What are the main findings? Response: Primary care physicians highly value access to advanced imaging: 88% of the PCPs indicated that advanced imaging increases their diagnostic confidence; 90% believe imaging provides data not otherwise available; 88% reported access to imaging  permits better clinical decision making;  88% reported increases confidence in treatment choices , and 86% say it shortens time to definitive diagnosis. Most  Primary care physicians ( 85%) believe that patient care would be negatively impacted without access to advanced imaging. One very interesting finding is in differences in attitudes and valuations in younger vs. older physicians towards advanced imaging modalities.  For the purposes of this part of the analysis we divided the survey respondents into those in practice 1-20 years and those practicing radiology more than 21 years.  Presumably those practicing less 21 years trained with ready access to advanced imaging versus those who presumably having practiced without ready access to the advanced imaging modalities of MRI, CT and PET. Respondents who have practiced without ready access attach higher value to the ability to shorten the time to definitive diagnosis, ability to replace invasive procedures, make better clinical decisions, and believe the quality of patient care would be negatively impacted without access to advanced imaging.  The younger physicians attach more value to the practice efficiency issues such as enabling the Primary care physician to see more patients, or patient centric issues like the ability to communicate on a visual level with the patient. (more…)
Author Interviews, Cognitive Issues, JAMA / 26.01.2015

Shelly L. Gray, PharmD, MS Professor of Pharmacy School of Pharmacy, University of Washington, SeattleMedicalResearch.com Interview with: Shelly L. Gray, PharmD, MS Professor of Pharmacy School of Pharmacy, University of Washington, Seattle Medical Research: What is the background for this study? What are the main findings? Dr. Gray: Many medications have anticholinergic effects such as those used to treat overactive bladder, seasonal allergies, and depression.  The general view is that anticholinergic-induced cognitive impairment is reversible, however, emerging evidence suggests that these medications may be associated with increased dementia risk.  We conducted a prospective population-based cohort study in 3434 older adults to examine whether cumulative anticholinergic medication use is associated with increased risk of incident dementia.  Using automated pharmacy data, we found that higher 10-year cumulative dose was associated with increased risk for dementia and Alzheimer disease over an average of 7.3 years of follow-up.  In particular, people with the highest use (e.g. taking the equivalent of oxybutynin 5 mg/day or chlorpheniramine 4 mg/day for longer than 3 years) were at greatest risk. (more…)
Author Interviews, JAMA, Ophthalmology / 26.01.2015

MedicalResearch.com Interview with: Simone L. Li, PhD Retina Foundation of the Southwest Dallas, Texas Medical Research: What is the background for this study? What are the main findings? Dr. Li: In a previous study, we found that binocular iPad game play significantly improved visual acuity in the amblyopic eye. The purpose of the current study was to determine the longevity of these effects and we found that the visual acuity improvements obtained with binocular iPad game play had been retained for at least 12 months after the treatment ended. (more…)
Author Interviews, FASEB, Genetic Research, Stanford / 26.01.2015

Dr. John Ramunas PhD Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, CaliforniaMedicalResearch.com Interview with: Dr. John Ramunas PhD Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, California Medical Research: What is the background for this study? Dr. Ramunas: Telomeres comprise repetitive DNA sequences at the ends of chromosomes.  Telomeres protect the ends of chromosomes, but become shorter with each cell division and due to oxidative damage.  Critically short telomeres are implicated in diseases of aging and devastating genetic disorders of insufficient telomere maintenance . Medical Research: What are the main findings? Dr. Ramunas: Our main finding is that telomeres in human cells can be lengthened by a new method with therapeutic potential.  We delivered modified mRNA encoding TERT, the protein component of telomerase, the enzyme that increases the length of telomeres by adding DNA repeats.  The protein TERT is usually the rate limiting component of the enzyme. In this study, we used four groups of cells.  The first group received modified mRNA encoding TERT, and the other three groups were controls that received either mRNA encoding an inactive form of TERT, the solution in which TERT is delivered, or no treatment.  The telomeres of the first group (telomere extending treatment group) were extended rapidly over a period of a few days, whereas the telomeres of the three control groups were not extended.  The first group was also able to undergo more cell divisions, whereas the controls were not.  Importantly for the potential safety of our approach, the telomeres of the first group resumed shortening after they were extended.  This is important because it shows that due to the short, transient treatment, the cells were not immortalized, ie. not tumorigenic. Further, all of the cell populations treated to date eventually stopped dividing, further indicating that they were not immortalized.  We have tested the approach on cell types including fibroblasts and myoblasts and are now testing it on stem cells. A surprising and exciting finding was that we could treat the cells several times with enhanced effects on the capacity of cells to divide.  For instance, after a first treatment, we saw an increase of 50,000-fold in cell numbers before cells stopped dividing, compared to untreated cells.  If we waited a few weeks and repeated this treatment, we saw a similar gain in cell division and number.  Since the increase in numbers is compounded with each treatment, a small sample of cells, for example from a small biopsy, can be amplified to very large numbers. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues / 26.01.2015

MedicalResearch.com Interview with: Craig S. Atwood Associate Professor, University of Wisconsin Madison, WI Richard L. Bowen, M.D. Private Practice, Charleston, SC Medical Research: What is the background for this study? Response: Currently, there is no treatment for Alzheimer’s disease that halts or slows its progression. Alzheimer’s disease is a neurodegenerative disorder resulting in memory loss and impairments of behavioral, language and visuo-spatial skills. A growing body of biological, preclinical and epidemiological data suggests that the age-related changes in hormones of the hypothalamic-pituitary-gonadal (HPG) axis are a major etiological factor in Alzheimer disease. The changes in these hormones include not only the decline in the sex steroids, (i.e. 17-estradiol and testosterone), but the elevations in gonadotropin-releasing hormone and luteinizing hormone. In particular there are encouraging epidemiological studies involving the use of Lupron Depot which suppresses these hormones. In one such study which included hundreds of thousands of patients it was found that men who had prostate disease and were treated with Lupron Depot had a 34 to 55 percent decreased risk of developing Alzheimer’s disease compared with prostate-cancer patients who didn’t receive the drug. (more…)
Author Interviews, Baylor College of Medicine Houston, Cognitive Issues, Sleep Disorders / 26.01.2015

Michael K. Scullin, Ph.D. Principal Investigator of the Sleep Neuroscience & Cognition (SNaC) Laboratory and an Assistant Professor of Psychology & Neuroscience Director Sleep Neuroscience and Cognition Laboratory Baylor UniversityMedicalResearch.com Interview with: Michael K. Scullin, Ph.D. Principal Investigator of the Sleep Neuroscience & Cognition (SNaC) Laboratory and an Assistant Professor of Psychology & Neuroscience Director Sleep Neuroscience and Cognition Laboratory Baylor University Medical Research: What is the background for this study? What are the main findings? Dr. Scullin: One of the purposes of sleep in healthy adults is to optimize cognitive functioning. When we lose out on a few hours of sleep we tend not to be able to focus or think as well as when we get enough sleep (typically 8 hours). Even more interesting is that particular aspects of sleep physiology—our deepest levels of sleep known as slow wave sleep and rapid eye movement sleep—are essential to our brain’s ability to take the information that we learn during the day and stabilize those memories so that we can use them in the future. Sleep quantity and quality change markedly across the lifespan, though there are individual differences in how much one’s sleep changes. Our work was concerned with the possible long-term repercussions of cutting back on sleep and getting lower quality sleep (less slow wave sleep and rapid eye movement sleep).  We reviewed approximately 200 scientific articles on this topic and we found that the amount of total sleep and the quality of that sleep is important to cognitive and memory functioning in young adults and middle-aged adults and can even predict how well someone’s cognitive functioning will be decades later. Thus, if you’re sleeping well when you are 40 then you are investing in preserving your mental functioning at age 50. (more…)
Antibiotic Resistance, Author Interviews, Infections / 26.01.2015

Anu Kantele, MD PhD Associate Professor, Department of Medicine, University of Helsinki Specialist of Infectious Diseases, Helsinki University Hospital Head of Travel Clinic, Aava Medical Centre "Photo taken by Leena Mattila/YLE/science"MedicalResearch.com Interview with: Anu Kantele, MD PhD Associate Professor, Department of Medicine, University of Helsinki Specialist of Infectious Diseases, Helsinki University Hospital Head of Travel Clinic, Aava Medical Centre Medical Research: What is the background for this study? What are the main findings? Dr. Kantele: Increasing antimicrobial resistance is considered a serious global threat for modern medicine. Resistance is rapidly surging in regions with poor hygiene and uncontrolled use of antibiotics. Resistant bacteria are gradually spreading from there to countries in which the prevalence has thus far been low. Our study was conducted among 430 healthy Finnish travelers visiting warm countries (tropical /subtropical regions). The volunteers provided stool samples before and after travel and filled in questionnaires. The stools were analyzed for multidrugresistant bacteria (not only so called ESBL bacteria but also CPE bacteria which are even more resistant). None of the travelers had CPE strains in their stools before or after their journey. 1% carried ESBL before travel, and 21% acquired a strain while overseas. The risk was greatest in the Indian subcontinent and almost similar in Southeast Asia. In Africa, it proved to be increased but did not reach such a high level. Two factors amplified the risk significantly: travellers’ diarrhea and use of antibiotics. Among the entire study population, ESBL was found in 11% of those staying healthy, 22% of those with diarrhea, and 37% of those who took antibiotics for their diarrhea. In the Indian subcontinent, the respective figures were 23%, 47%, and 80%, and in Southeast Asia 14%, 32%, and 69%. Medical Research: Why do antibiotics predispose to contracting resistant bacteria from the surroundings? Dr. Kantele: The effects of antibiotics cannot be restricted to killing merely the bugs we wish them to kill. When doing their job they also wipe out a huge number of our own intestinal bacteria, thereby opening the door for newcomers’ invasion. If antibiotics are taken in an environment exposing people to a multitude of resistant bacteria, part of these newcomers are likely to be resistant ones. Antibiotics may, in fact, kill the sensitive newcomers and favor the resistant ones. (more…)
Antibiotic Resistance, Author Interviews, Infections / 26.01.2015

Dr. Thiago César Nascimento Assistant Professor, Department of Basic Nursing Laboratory of Bacterial Physiology and Molecular Genetics Institute of Biological Sciences Federal University of Juiz de Fora, BrazilMedicalResearch.com Interview with: Dr. Thiago César Nascimento Assistant Professor, Department of Basic Nursing Laboratory of Bacterial Physiology and Molecular Genetics Institute of Biological Sciences Federal University of Juiz de Fora, Brazil Medical Research: What is the background for this study? What are the main findings? Response: Preliminarily, we observed a high incidence of coagulase-negative  Staphylococcus  strains (CoNS) recovered from the leachate of the health care waste in an untreated sanitary landfill. As Staphylococcus sp. especially oxacillin or methicillin-resistant CoNS remains as important putative pathogenic bacteria regarding human and other animals, in this study we investigated the antimicrobial susceptibility patterns and the occurrence of the  mecA  gene. In conclusion, our results raise issues related to the viability of putative pathogenic bacteria resistant to important antimicrobial drugs carrying important resistance markers in untreated healthcare waste in sanitary landfills.These risks regarding the potential spread of leachate from sanitary landfills due to human and animal activities, or even due to weather phenomena, such as torrential rains and floods, should be considered. Our results address a phenomenon related to the incorrect healthcare waste management in Brazil and in other geographical regions. Taking into account environmental health, more conscientious  policies should be considered by authorities to avoid the disposal of healthcare waste without any further treatment. (more…)
Author Interviews, Genetic Research / 26.01.2015

MedicalResearch.com Interview with: Joao Pedro de Magalhaes, PhD Institute of Integrative Biology Biosciences Building, Room 245 University of Liverpool UK Integrative Genomics of Ageing Group: http://pcwww.liv.ac.uk/~aging/ Medical Research: What is the background for this study? What are the main findings? Response: Our understanding of species differences in longevity (e.g., why can mice not live more than 5 years or dogs more than 30, yet bats can live over 40 years, humans over a century and bowheads over two centuries) is very poor and thus our findings provide novel candidate genes and mechanisms for future studies. The candidate genes we found with evidence of bowhead-specific functions may play a role in the exceptional longevity and disease resistance of these animals. In particular, we discovered changes in bowhead genes related to cell cycle, DNA repair, cancer, and aging that suggest alterations that may be biologically-relevant.  So my own view is that this points toward improved DNA repair and cell cycle regulation mechanisms to prevent DNA damage accumulation during the lifescourse which in turn promotes longevity and resistance to age-related diseases like cancer. (more…)
Author Interviews, Breast Cancer, Karolinski Institute / 26.01.2015

Dr Jingmei Li Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, SwedenMedicalResearch.com Interview with: Dr Jingmei Li Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, Sweden Medical Research: What is the background for this study? What are the main findings? Response: Some cancers, such as interval breast cancers, which are detected within two years of a negative mammogram, are associated with more aggressive tumour characteristics and worse prognosis. As women with interval cancers were twice as likely to have a personal of family history of breast cancer, it is likely that there exist inherited variants that predispose a woman to the more aggressive form of the disease. Our study is one of the first to show empirical evidence that screen-detected and interval cancers are different genetically and are two distinct subtypes. (more…)
Author Interviews, Cost of Health Care, NEJM, University of Pennsylvania / 26.01.2015

Daniel Polsky PhD Executive Director, Leonard Davis Institute of Health Economics Professor of Medicine and Health Care Management Perelman School of Medicine and the Wharton School University of PennsylvaniaMedicalResearch.com Interview with: Daniel Polsky PhD Executive Director, Leonard Davis Institute of Health Economics Professor of Medicine and Health Care Management Perelman School of Medicine and the Wharton School University of Pennsylvania Medical Research: What is the background for this study? What are the main findings? Dr. Polsky: The Medicaid Fee bump, a provision of the Affordable Care Act (ACA), raised Medicaid payments to Medicare levels in 2013 and 2014 for selected services and providers expired on January 1, 2015 before policymakers had much empirical evidence about its effects.   The federally funded increase in reimbursements was aimed at expanding access to primary care for the growing number of Medicaid enrollees. The reimbursement increase expired at the end of 2014 in most states.  We found that this policy worked to increase the number of providers offering primary care appointments to Medicaid patients.  The Medicaid pay bump was associated with a 7.7 percentage points increase in new patient appointment availability without longer wait times.   This increase in availability was largest in the states where primary care physicians received the largest increase in their Medicaid reimbursements. (more…)
Author Interviews, Blood Pressure - Hypertension, BMJ, Heart Disease / 25.01.2015

MedicalResearch.com Interview with: Dr. Maria Guzman-Castillo Department of Public Health and Policy University of Liverpool, Liverpool, UK Medical Research: What is the background for this study? What are the main findings? Dr. Guzman-Castillo: The UK has experienced a remarkable 60% reduction in coronary heart disease (CHD) mortality since the 1970s. However CHD remains the leading cause of premature death. The aim of our study was to analyse the recent falls in coronary heart disease mortality and quantify the relative contributions from preventive medications and from population-wide changes in blood pressure and cholesterol levels, particularly exploring the potential effects on socioeconomic inequalities, an aspect not well explored in the past. Our study found that, approximately 22,500 fewer deaths were attributable to reductions in blood pressure and cholesterol in the English population between 2000-2007. The substantial decline in blood pressure was responsible for approximately 13,000 fewer deaths. Approximately 1,800 fewer deaths came from medications and some 11,200 fewer deaths from population-wide changes. Reduction in population blood pressure fewer deaths in the most deprived quintile compared with the most affluent. Reduction in cholesterol resulted in substantially smaller gains, approximately 7,400 fewer deaths; approximately 5,300 fewer deaths were attributable to statin use and approximately 2,100 DPPs to population-wide changes. Interestingly, statins prevented more deaths in the most affluent quintile compared with the most deprived. Conversely, population-wide changes in cholesterol prevented threefold more deaths in the most deprived quintile compared with the most affluent. (more…)
Author Interviews, OBGYNE, PLoS / 25.01.2015

Charles Morrison PhD FHI 360 Clinical Sciences Durham, North CarolinaMedicalResearch.com Interview with: Charles Morrison PhD FHI 360 Clinical Sciences Durham, North Carolina MedicalResearch: What is the background for this study? What are the main findings? Dr. Morrison: The possible connection between hormonal contraception and HIV acquisition has been an open question for 25 years. Some studies have suggested that there is an increased risk associated with hormonal contraception, particularly with the 3-month injectable contraceptive called depot-medroxyprogesterone acetate (DMPA). Other studies have found that no such risk exists. The World Health Organization (WHO) has held several technical consultations on this subject. WHO’s current guidelines state that “because of the inconclusive nature of the body of evidence on the possible increased risk of HIV acquisition, women using progestogen-only injectable contraception should be strongly advised to also always use condoms, male or female, and other HIV preventive measures.” Two meta-analyses focusing on hormonal contraception and HIV acquisition have recently been published. One of them, FHI 360’s collaborative study, is an individual participant data meta-analysis. It found that users of injectable DMPA were 50 percent more likely to become infected with HIV than women not using hormonal contraceptives. For women using a different injectable progestin, norethisterone enanthate (NET-EN), or combined oral contraceptives (COC), the study investigators did not find a significantly increased risk of acquiring HIV compared to those who were not using hormonal contraceptives. Furthermore, DMPA users were 43 percent and 32 percent more likely to become infected with HIV compared to oral contraceptives users and NET-EN users, respectively. It is important to point out a key secondary finding. The associations between hormonal contraception and risk of becoming infected with HIV were attenuated in studies that had a lower risk of methodological bias compared to those with higher risk of bias. This suggests that some of the risk found to be associated with hormonal contraception in fact may be attributed to inherent flaws in the nonrandomized studies themselves. (more…)
Author Interviews, Genetic Research, Melanoma, Nature / 25.01.2015

MedicalResearch.com Interview with: Prof Lukas Sommer. Ph.D. Cell and Developmental Biology University of Zurich Institute of Anatomy Zurich Switzerland MedicalResearch: What is the background for this study? What are the main findings? Prof. Lukas Sommer:   Melanoma, the most aggressive of all skin cancers, is often fatal for patients due to the pronounced formation of metastases. Up to date, a melanoma’s rampant growth was mainly attributed to genetic causes, such as mutations in certain genes. However, we now reveal that so-called epigenetic factors also play a crucial role in the formation of metastases in malignant skin cancer. Epigenetic factors do not influence the gene sequence directly, but rather cause certain genes and chromosomal segments to be packed in different densities – and thus make them accessible for reading. In our study we identified “EZH2” as an epigenetic control protein found very frequently in malignant melanoma cells compared to normal cells. In these cells, “EZH2” controls genes that govern both tumor growth and genes that are important for the formation of metastases. We exploited this central position of EZH2 to combat the cancer by using a pharmacological inhibitor to suppress the activity of EZH2. As a result, we were able to prevent the growth and malignant spread of the cancer in an animal model and in human melanoma cells. (more…)
Author Interviews, Heart Disease, JACC, Outcomes & Safety / 25.01.2015

Herbert Aronow, MDMedicalResearch.com Interview with: Herbert D. Aronow, MD, MPH, FACC, FSCAI, FSVM Governor, American College of Cardiology (ACC) – Michigan Chapter Chair, ACC Peripheral Vascular Disease Section Trustee, Society for Vascular Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Aronow: Psychomotor and cognitive performance may be impaired by sleep deprivation.  Interventional cardiologists perform emergent, middle-of-the-night procedures, and may be sleep-deprived as a consequence.  Whether performance of middle-of-the-night percutaneous coronary intervention (PCI) procedures impacts outcomes associated with PCI procedures performed the following day is not known.  (more…)
Author Interviews, BMJ, Gastrointestinal Disease, Pediatrics / 25.01.2015

Dr Laila J Tata PhD Associate Professor in Epidemiology Faculty of Medicine & Health Sciences University of NottinghamMedicalResearch.com Interview with: Dr Laila J Tata PhD Associate Professor in Epidemiology Faculty of Medicine & Health Sciences University of Nottingham Medical Research: What is the background for this study? What are the main findings? Response: Over the last decades there has been increased clinical awareness of coeliac disease (CD) partially because of improvements in the accuracy and availability of diagnostic tests, however, we do not have current estimates of actual celiac disease diagnoses in children and it is important to know whether diagnostic patterns vary socioeconomic group. Funded by CORE/Coeliac UK and conducted at the University of Nottingham, this study analysed 2,063,421 children aged less than 18 years who were registered with general practices (primary care doctors) across the United Kingdom contributing to their routine electronic health records to The Health Improvement Network (THIN) database  between 1993 and 2012. The study found 1,247 children were diagnosed with coeliac disease, corresponding to about 1 new case in every 10,000 children each year. Girls consistently had more diagnoses than boys and whilst the incidence of new celiac disease cases among children up to age 2 years remained stable over time, diagnoses in older children almost tripled over the past 20 years. Moreover, the study found a socioeconomic gradient in celiac disease diagnoses, such that children living in less socioeconomically deprived areas were about twice as likely to be diagnosed as those from more deprived areas. This pattern held for boys and girls and for all ages. (more…)
Allergies, Author Interviews, Dermatology / 25.01.2015

Dr. Alan Irvine, MD Professor in Dermatology Department of Clinical Medicine Trinity College DublinMedicalResearch.com Interview with: Dr. Alan Irvine, MD Professor in Dermatology Department of Clinical Medicine Trinity College Dublin   Medical Research: What is the background for this study? What are the main findings? Response: Atopic diseases include atopic dermatitis (AD, also know as eczema), food allergy, allergic rhinitis and asthma.  The prevalence of these diseases has increased in recent decades causing considerable morbidity in childhood. The putative “Atopic March” refers to the typical sequence of clinical manifestation of atopic disease, usually initiated by atopic dermatitis from early infancy. Parental atopy is an independent risk factor for development of atopic disease. The genetic mechanisms and inheritance pattern of atopic diseases are not fully elucidated but recent candidate gene studies and Genome Wide Association Studies (GWAS) have yielded some insights. The most widely replicated and most significant gene to influence atopic dermatitis is Filaggrin (FLG). Filaggrin is a filament binding protein in the stratum Corneum. FLG loss-of-function mutations (FLG mut) occur in 10% of Europeans, imparting an increased risk of atopic dermatitis, food allergy and asthma.  The overall increase in risk of atopic dermatitis conferred by a single FLG loss-of-function mutation is approximately 3.3, with a significant additional and independent effect conferred by intragenic copy number variations in FLG. Importantly FLG mutations increase the risk of developing asthma only in the presence of atopic dermatitis. While loss-of-function mutations in the skin barrier protein filaggrin (FLG) are a major risk for atopic dermatitis, the pathogenic sequence of disturbances in skin barrier function prior to or during the early development of atopic dermatitis is not fully understood. A more detailed understanding of these events is needed to develop a clearer picture of disease pathogenesis. A robust, non-invasive test to identify babies at high risk of atopic dermatitis would be important in planning early intervention and/or prevention studies. We found that raised transepidermal water loss at birth and at two months in asymptomatic infants predates the development of atopic dermatitis. This signal is independent of FLG status and parental atopy. (more…)
Author Interviews, Breast Cancer, Scripps / 25.01.2015

Dr. Patrick Griffin PhD Professor and Chairman Department of Molecular Therapeutics Director of the Translational Research Institute Scripps Research Institute, Jupiter, FloridaMedicalResearch.com Interview with: Dr. Patrick Griffin PhD Professor and Chairman Department of Molecular Therapeutics Director of the Translational Research Institute Scripps Research Institute, Jupiter, Florida MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Griffin: We identified a novel synthetic compound known as SR1848 that sharply inhibits the activity and expression of “liver receptor homolog-1” or LRH-1, a protein that plays an important role in the progression of breast and pancreatic cancers. Our new study shows that SR1848 removes LRH1 from DNA, shutting down expression of LRH-1 target genes, and halts cell proliferation. It’s a novel compound that appears to be a promising chemical scaffold for fighting tumors that are non-responsive to standard therapies. (more…)
Author Interviews, Genetic Research, Mental Health Research, Scripps / 25.01.2015

Dr. Gavin Rumbaug Professor (Associate) The Scripps Research InstituteMedicalResearch.com Interview with: Gavin Rumbaug Professor (Associate) The Scripps Research Institute Medical Research: What is the background for this study? What are the main findings? Response: We have developed a genetic approach that protects animal models against a type of genetic disruption that causes intellectual disability, including serious memory impairments and altered anxiety levels. The findings focus on treating the effects of mutations to a gene known as Syngap1. In our new study, we examined the effect of damaging Syngap1 mutations during development and found that the mutations disrupt a critical period of neuronal growth—a period between the first and third postnatal weeks in mouse models. We found that a certain type of cortical neuron grows too quickly in early development, which then leads to the premature formation of certain types of neural circuits. These findings help explain why genetic treatments in adult mice are not very effective. (more…)
Author Interviews, CDC, OBGYNE, Opiods / 25.01.2015

Dr. Jennifer Lind PharmD, MPH Division of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities, CDCMedicalResearch.com Interview with: Dr. Jennifer Lind PharmD, MPH Division of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities, CDC Medical Research: What is the background for this study? Dr. Lind:  CDC researchers published a new study estimating the proportion of women aged 15-44 years who filled a prescription for opioid pain medications.  Opioids are prescribed by healthcare providers to treat moderate to severe pain. They are also found in some prescription cough medications. Opioids include medications like codeine, oxycodone, hydrocodone, or morphine. For this study, researchers used data from two large insurance claims datasets—one on Medicaid and one on private insurance—and looked at data from 2008-2012. Medical Research: What are the main findings? Dr. Lind: Opioid medications are widely used among women of reproductive age in the United States, regardless of insurance type. On average, more than a third (39 percent) of women aged 15-44 years enrolled in Medicaid, and more than one fourth (28 percent) of those with private insurance filled a prescription for an opioid pain medication each year during 2008-2012. Taking these medications early in pregnancy, often before women know they are pregnant, can increase the risk for some birth defects (such as spina bifida) and other poor pregnancy outcomes (such as preterm birth or low birth weight). (more…)
Asthma, Author Interviews, CHEST, Omega-3 Fatty Acids / 23.01.2015

John Brannan PhD Firestone Institute for Respiratory Health at St Joseph’s Healthcare & McMaster University, Hamilton, Ontario, CanadaMedicalResearch.com Interview with: John Brannan PhD Firestone Institute for Respiratory Health at St Joseph’s Healthcare & McMaster University, Hamilton, Ontario, Canada Medical Research: What is the background for this study? Response: The use of omega-3 acid supplements as treatments for allergic diseases including asthma is controversial. Studies by investigators from Indiana University in the USA have repeatedly demonstrated a beneficial effect of high dose omega-3 fatty acid supplements over 3 weeks in attenuating exercise-induced bronchoconstriction (EIB) similar or possibly better in potency to what may be expected with a regular inhaled corticosteroids. The study by Brannan et al. attempted to validate these findings by using inhaled mannitol, a bronchial provocation test that was derived from the understanding of exercise-induced bronchoconstriction and which has demonstrated experimentally to be a useful model for exercise-induced bronchoconstriction. All pharmacotherapies that modify exercise-induced bronchoconstriction can modify the airway sensitivity to inhaled mannitol in persons with asthma, thus it was of interest to see if an 'alternative' treatment that demonstrated efficacy in exercise-induced bronchoconstriction could too modify the airway response to mannitol. Medical Research: What are the main findings? Response: The main findings were, to our surprise, there was no benefit of high dose omega-3 fatty acid supplements on bronchial hyperresponsiveness to mannitol over 3 weeks. This was associated with no changes in airway inflammation (sputum eosinophils), lung function or asthma symptom control. We also found no benefit on resting urinary mast cell metabolites, in contrast to the findings in studies showing a benefit of omega-3 fatty acids on EIB. Our findings suggest that omega-3 supplements in tissues may not be able to penetrate tissue and/or modify the substrate flow of eicosanoids in tissue such as the airways of the asthmatic. We did observed the expected reductions in blood triglycerides which suggests that these doses of omega-3s can modify metabolism in the blood or to some extent tissues that are highly perfused. (more…)
Author Interviews, BMJ, Exercise - Fitness / 23.01.2015

Sarah Hanson Norwich Medical School University of East AngliaMedicalResearch.com Interview with: Sarah Hanson Norwich Medical School University of East Anglia Medical Research: What is the background for this study? What are the main findings? Response: Physical inactivity is a global problem. Walking is an easy way to increase physical activity. One way to increase physical activity may be through the use of outdoor walking groups. Walking groups are increasingly popular but until now we have not known if there are wider health benefits from walking groups, apart from increasing physical activity. Medical Research: What was the study method? Response: A systematic review and meta-analysis of outdoor walking group interventions found 42 studies which met the eligibility criteria. These studies involved 1,843 participants in 14 countries doing approximately 74,000 hours of walking. (more…)
Author Interviews, Heart Disease, Outcomes & Safety, Surgical Research / 23.01.2015

MedicalResearch.com Interview with: Keita Morikane, Director Division of Clinical Laboratory and Infection Control Yamagata University Hospital Medical Research: What is the background for this study? What are the main findings? Response: The risk factors for surgical site infection following cardiac surgery is extensively investigated, but those specifically of open heart surgery or coronary artery bypass remains unknown. The main findings were that the risk factors between the two types of cardiac surgery were considerably different. (more…)
Author Interviews, Diabetes, PLoS / 23.01.2015

Dr. Holger Rehmann Department of Molecular Cancer Research UMC Utrecht The NetherlandsMedicalResearch.com Interview with: Dr. Holger Rehmann Department of Molecular Cancer Research UMC Utrecht The Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. Rehmann: We have developed a chemical modified version of the second messenger cAMP, Sp-8-BnT-cAMPS that allows selective activation of Epac2, a protein that augments glucose induced insulin secretion. The second messenger cAMP activates a couple of receptor proteins, which controls such divergent physiological effects as gene transcription, pacemaker activity, olfaction, and cell adhesion. Almost any cell responses in one or the other way to cAMP and thus selective action on only one cAMP receptor would be a requirement for a drug to induce specific effects. The study confirms that it is possible to pharmacologically discriminate between structurally highly related cAMP receptors. And indeed, Sp-8-BnT-cAMPS augments glucose induced insulin secretion in primary human islets. Epac2 is thus a putative target for the development of an antidiabetic drug. (more…)
Author Interviews, Neurological Disorders, Neurology, Pediatrics, Sleep Disorders / 23.01.2015

James Tao, MD, Ph.D Assistant Professor Director, EEG Lab Department of Neurology, The University of Chicago, IL.MedicalResearch.com Interview with: James Tao, MD, Ph.D Assistant Professor Director, EEG Lab Department of Neurology, The University of Chicago, IL. Medical Research: What is the background for this study? What are the main findings? Dr. Tao: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of mortality in patients with chronic uncontrolled epilepsy. Patients often died in sleep, in bed, and unwitnessed. They were often found in prone position. These circumstances of SUDEP are remarkably similar to those of sudden infant death syndrome (SIDS). In our study, we found that 73% of 253 SUDEP patients were died in prone position. These findings suggest that sudden unexpected death in epilepsy may share the mechanisms similar to SIDS. (more…)
Author Interviews, JAMA, Mental Health Research / 23.01.2015

MedicalResearch.com Interview with: David P.G. van den Berg PhD student Clinical Psychologist Cognitive behavioural therapist Parnassia Psychiatric Institute Early Detection and Intervention Team (EDIT) Zoutkeetsingel, The Netherlands Medical Research: What is the background for this study? What are the main findings? Response: The last decade it has become clear that many people with psychotic disorders suffered severe childhood trauma. These experiences enhance chances of developing psychosis, but also result in comorbid posttraumatic stress disorder (PTSD). PTSD is highly prevalent in patients with psychotic disorders and negatively influences prognosis and wellbeing. Prolonged Exposure (PE) and Eye Movement Desensitization and Reprocessing (EMDR) are highly effective treatments and recommended as first choice treatments in PTSD guidelines worldwide. Although there is no evidence to support this, patients with psychosis are excluded from PTSD treatment due to fear of destabilization or psychotic decompensation. Moreover, psychosis is the most used exclusion criterion in PTSD trials. This is the first randomized clinical trial (RCT) of the efficacy of PTSD treatment in psychosis. In this RCT 155 patients with a psychotic disorder and comorbid PTSD were randomly assigned to PE, EMDR or Waiting List (WL). In the treatment conditions participants received 8 sessions of 90-minutes therapy. Standard protocols were used. Treatment was not preceded by stabilizing psychotherapeutic interventions or skills training. The first session comprised psycho-education about PTSD and target selection. In sessions 2 to 8 traumas were treated, starting with the most distressing experience. Baseline, post-treatment and 6-month follow-up assessments were made. Participants in both PE and EMDR showed greater reduction of PTSD symptoms than those in WL. Between group effect sizes were large. About sixty percent of the participants in the treatment groups achieved loss of diagnosis. Treatment effects were maintained at six-month follow-up for both PE and EMDR. Treatments did not result in serious adversities. (more…)